This application from The University of Tennessee Health Science Center (UTHSC) requests funds to construct a Regional Biocontainment Laboratory (RBL) facility and vivarium that will serve members of the Region 4 Research Center of Excellence (RCE) and, more broadly, researchers from major institutions from Maine to Minnesota (Regions 1, 3, 5, and 6). The facility will consist of a suite of biosafety levels (BSL) -2 and -3 laboratory modules, space for training, security, and substantial vivarium space. The RBL will adjoin our main research vivarium in the center of the Health Science campus. Our plans have accounted for surge capacity. These facilities will permit researchers to efficiently initiate and complete research on Class A pathogens. Strong technical support and training will ensure safety of all experiments. This application has strong support from leaders of our RCE Region 4 application (Dr. Barton Haynes), Region 5 (Dr. Patrick Schlievert), the Center for Disease Control and the Southeastern Center for Emerging Biologic Threats (Dr. David Stephens). Letters are appended. We are especially pleased as part of this application to have established a strong collaboration with the Jackson Laboratory (TJL). The inter-institutional and multidisciplinary collaboration between groups with genetics and infectious disease expertise will ensure widespread use of hundreds of novel mouse strains in the Memphis RBL facility. Biodefense-related research conducted using our joint UTHSC/TJL-RCE4 facility will provide critical new knowledge on mechanisms and genetic factors that influence how bacteria and viruses cause disease in mouse and humans. We expect that the collaborative research and discoveries that arise from use of this RBL facility will lead to effective prophylaxis, inoculation, treatment, and perhaps even eradication of virulent diseases. We intend that the research resources and genetics expertise will be available through our RBL facility to be part of NIAID's Biodefense agenda and part of the federal government's Biodefense initiative. This facility has been designed as a regional and a national facility with a special emphasis on the genetics of complex interactions between pathogens and the mammalian immune system. We are open to additional collaborations and resource sharing with other RBLs and NBLs. In recent years, the laboratory mouse has emerged as a powerful model for exploring mechanisms of infectious disease. Recent progress by two of our RBL consortium members, W. Dietrich and J. Mountz, are particularly good examples. The utility of mouse models has accelerated now that full sequence data are available for four strains of mice. It is routinely possible to modify the mouse genome and to make responses to pathogens more human-like. In-depth analyses of normal, mutant, humanized, and recombinant inbred strains of mice to infectious agents herald an unprecedented increase in our understanding of the complexity of pathogen-host relationships. UTHSC is now an internationally recognized center for mouse genetics. Leaders of two research consortia--the Tennessee Mouse Genome Consortium and the Complex Trait Consortium, Drs. Dan Goldowitz and Robert W. Williams, are senior faculty in the Center of Genomics and Bioinformatics at UTHSC. Both investigators oversee large collaborative multi-institutional research programs that generate hundreds of novel mutant mice, recombinant lines, and bioinformatics resources. In addition, UTHSC now boasts a world-class team of researchers in the field of infectious disease headed by Dr. Gerald Byrne, chairman of the Department of Molecular Sciences, Dr. Malak Kotb, and Dr. James Dale. Dr. Byrne and colleagues have recently assembled a Center of Excellence in Bacterial Pathogenesis. Complementing and augmenting the infectious diseases program at UTHSC we are fortunate to collaborate with a strong program at St. Jude Children's Research Hospital lead by Dr. Elaine Tuomanen. Finally, in addition to numerous collaborations with investigators at UNC Chapel Hill, UAB, Duke, Vanderbilt and other RCE 4 lead institutions, we have forged collaborations with the Oak Ridge National Laboratory, the CDC, and several private and public ventures within the mid-South region. The most significant of these commercial collaborators is Large Scale Biology Inc., Viral Antigen Inc., Genotherapeutics Inc, and Ramsafe Technologies LLC. Collectively this RBL will be an exemplary regional resource and strong national resource for immunogenetic studies of bioterrorism agents. This application meets all six of the eligibility requirements assurances set forth in BAA.